The overall goal of this project is to define the pathophysiologic mechanism through which antiphospholipid antibodies (aPL) act as risk factors for vascular disease. The hypothesis is that aPL are predictors of ischemic stroke and myocardial infarction (MI) in elderly men and women, yet are not associated with progression of atherosclerosis. A nested case-control study is proposed within the Cardiovascular Health Study (CHS) cohort (5,201 men and women) and CHS African-American cohort (687 men and women). Stored frozen baseline sera and cardiovascular risk factor data including measures of hemostasis and inflammation and change in intimal-medial thickness (IMT) are already available on all study participants. The study population, all 65 years or older at baseline, will consist of 370 cases with incident ischemic stroke, 370 cases with incident MI, and 1,480 race-matched controls. To allow stratification by race in the analyses of aPL as predictors of progression of subclinical atherosclerosis, an additional 300 persons without a history of stroke or MI will be sampled from the African-American cohort. Blood will also be sent to the University of Texas at San Antonio for state-of-the-art aPL determinations. Logistic and linear regression models will be used to test major study hypotheses. The results of this study will confirm the role of aPL as major risk factors for clinical and subclinical vascular diseasse in elderly men and women and determine whether the association with vascular disease is mediated by other known risk factors. These findings will be vital in the design of future studies that seek to clarify the relationship of the immune system to vascular disease.